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糖尿病护理中的吡啶甲酸铬疗法:分子和亚细胞分析揭示了个体预后预测、个性化治疗算法及新指南的必要性。

Chromium-picolinate therapy in diabetes care: molecular and subcellular profiling revealed a necessity for individual outcome prediction, personalised treatment algorithms and new guidelines.

作者信息

Yeghiazaryan Kristina, Peeva Viktoriya, Shenoy Aparna, Schild Hans H, Golubnitschaja Olga

机构信息

Department of Radiology, Rheinische Friedrich-Wilhelms-University of Bonn, Sigmund-Freud-Strasse 25, Bonn, Germany.

出版信息

Infect Disord Drug Targets. 2011 Apr;11(2):188-95. doi: 10.2174/187152611795589717.

Abstract

AIMS

Global figures clearly demonstrate inadequacy of current diabetes care: every 10 seconds one patient dies of diabetes-related pathologies. Nephropathy is the leading secondary complication of the disease. Nutritional supplement by chromium-picolinate is assumed to have beneficial therapeutic effects. However, potential toxic effects reported increase concerns about safety of chromium-picolinate. The experimental design aimed at determining, whether the treatment with clinically relevant doses of chromium-picolinate can harm through DNA damage and extensive alterations in central detoxification / cell-cycle regulating pathways in treatment of diabetes.

METHODS

Well-acknowledged animal model of db/db-mice and clinically relevant doses of chromium-picolinate were used. As an index of DNA-damage, measurement of DNA-breaks was performed using "Comet Assay"-analysis. Individual and group-specific expression patterns of SOD-1 and P53 were evaluated to give a clue about central detoxification and cell-cycle regulating pathways under treatment conditions. The study was performed in a double-blind manner.

RESULTS

Experimental data revealed highly individual reaction under treatment conditions. However, group-specific patterns were monitored: highest amount of damaged DNA--under the longest treatment with high doses, in contrast to groups with low doses of chromium-picolinate. Comet patterns were intermediate between untreated diabetised and control animals. Expression patterns demonstrated a correlation with subcellular imaging and dosage-dependent suppression under chromium-picolinate treatment.

CONCLUSIONS

This article highlights possible risks for individual long-term effects, when chromium-picolinate is used freely as a therapeutic nutritional modality agent without application of advanced diagnostic tools to predict risks and individual outcomes. Targeted measures require a creation of new guidelines for advanced Diabetes care.

摘要

目的

全球数据清楚地表明当前糖尿病护理存在不足:每10秒钟就有一名患者死于糖尿病相关病症。肾病是该疾病的主要继发性并发症。假定补充吡啶甲酸铬具有有益的治疗效果。然而,所报道的潜在毒性作用增加了人们对吡啶甲酸铬安全性的担忧。该实验设计旨在确定,在糖尿病治疗中,使用临床相关剂量的吡啶甲酸铬进行治疗是否会通过DNA损伤以及中枢解毒/细胞周期调节途径的广泛改变而造成损害。

方法

使用公认的db/db小鼠动物模型和临床相关剂量的吡啶甲酸铬。作为DNA损伤的指标,使用“彗星试验”分析进行DNA断裂的测量。评估超氧化物歧化酶-1(SOD-1)和P53的个体及组特异性表达模式,以了解治疗条件下中枢解毒和细胞周期调节途径的情况。该研究以双盲方式进行。

结果

实验数据显示在治疗条件下存在高度个体反应。然而,监测到了组特异性模式:与低剂量吡啶甲酸铬组相比,高剂量最长时间治疗组的受损DNA量最高。彗星试验模式介于未治疗的糖尿病动物和对照动物之间。表达模式显示与亚细胞成像以及吡啶甲酸铬治疗下的剂量依赖性抑制相关。

结论

本文强调了在没有应用先进诊断工具来预测风险和个体结果的情况下,随意将吡啶甲酸铬用作治疗性营养制剂时,个体长期影响可能存在的风险。针对性措施需要制定新的晚期糖尿病护理指南。

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